rs547154

Variant names:

Variant summary

Our verdict is The variant received -4 classification points (ACGS-UK Somatic Oncogenicity v2025). B1_Strong

The NM_000063.6(C2):c.1360+62G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.1 (AC=161,196) in the gnomAD database across 1,612,262 control chromosomes, including 8,996 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.187. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain Significance (no review stars).

Frequency

Genomes: 𝑓 0.12 ( 1195 hom., cov: 31)

Exomes 𝑓: 0.098 ( 7801 hom. )

Consequence

C2
NM_000063.6 intron

Scores

Clinical Significance

protective no assertion criteria provided B:1

Conservation

PhyloP100: -0.537

Publications

87 publications found

Variant links:

Genes affected

C2 (HGNC:1248): (complement C2) Component C2 is a serum glycoprotein that functions as part of the classical pathway of the complement system. Activated C1 cleaves C2 into C2a and C2b. The serine proteinase C2a then combines with complement factor 4b to create the C3 or C5 convertase. Deficiency of C2 has been reported to associated with certain autoimmune diseases and SNPs in this gene have been associated with altered susceptibility to age-related macular degeneration. This gene localizes within the class III region of the MHC on the short arm of chromosome 6. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described in publications but their full-length sequence has not been determined.[provided by RefSeq, Mar 2009]

C2 Gene-Disease associations (from GenCC):

complement component 2 deficiency
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

C2 links:

ENSG00000244255 (HGNC:):

ENSG00000244255 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000063.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 points.

GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.187 — exceeds 1% threshold (B1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_000063.6. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
C2	NM_000063.6	MANE Select	c.1360+62G>T	intron	N/A	NP_000054.2
C2	NM_001282458.2		c.1273+62G>T	intron	N/A	NP_001269387.1	A0A0G2JL69
C2	NM_001145903.3		c.964+62G>T	intron	N/A	NP_001139375.1	P06681-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
C2	ENST00000299367.10	TSL:1 MANE Select	c.1360+62G>T	intron	N/A	ENSP00000299367.5	P06681-1
ENSG00000244255	ENST00000456570.5	TSL:2	c.901+62G>T	intron	N/A	ENSP00000410815.1	K9J7H5
ENSG00000244255	ENST00000477310.1	TSL:5	c.674-64G>T	intron	N/A	ENSP00000418996.1	E7ETN3

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17723

AN:

151974

Hom.:

1197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.190

Gnomad AMI

AF:

0.0462

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.0571

Gnomad EAS

AF:

0.0617

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.0568

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0908

Gnomad OTH

AF:

0.131

GnomAD4 exome

AF:

0.0982

AC:

143452

AN:

1460170

Hom.:

7801

Cov.:

AF XY:

0.0993

AC XY:

72139

AN XY:

726438

show subpopulations

African (AFR)

AF:

0.188

AC:

6306

AN:

33472

American (AMR)

AF:

0.0738

AC:

3302

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0555

AC:

1451

AN:

26134

East Asian (EAS)

AF:

0.0736

AC:

2922

AN:

39694

South Asian (SAS)

AF:

0.156

AC:

13485

AN:

86246

European-Finnish (FIN)

AF:

0.0651

AC:

3405

AN:

52290

Middle Eastern (MID)

AF:

0.0713

AC:

411

AN:

5762

European-Non Finnish (NFE)

AF:

0.0950

AC:

105567

AN:

1111488

Other (OTH)

AF:

0.109

AC:

6603

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

8230

16460

24691

32921

41151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4056

8112

12168

16224

20280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.117

AC:

17744

AN:

152092

Hom.:

1195

Cov.:

AF XY:

0.114

AC XY:

8509

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.190

AC:

7876

AN:

41440

American (AMR)

AF:

0.101

AC:

1542

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0571

AC:

198

AN:

3468

East Asian (EAS)

AF:

0.0617

AC:

319

AN:

5172

South Asian (SAS)

AF:

0.143

AC:

689

AN:

4828

European-Finnish (FIN)

AF:

0.0568

AC:

602

AN:

10602

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0908

AC:

6174

AN:

67984

Other (OTH)

AF:

0.130

AC:

274

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

763

1526

2288

3051

3814

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

368

552

736

920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.102

Hom.:

1816

Bravo

AF:

0.124

Asia WGS

AF:

0.154

AC:

535

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.0956

AC:

11718

AN:

122554

Turkish Variome

AF:

0.0750

AC:

116

AN:

1546

Hom.:

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.0588

AC:

527

AN:

8960

Hom.:

ABraOM SABE-WGS-1171

AF:

0.120

AC:

282

AN:

2342

Hom.:

ClinVar

ClinVar submissions

Significance:protective

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Age related macular degeneration 14 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.70

(source)

DANN

Benign

0.76

PhyloP100

-0.54

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACGS-UK Somatic Oncogenicity v2025

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over